SARS-CoV-2 spreads via droplets, aerosols, and smear infection. From the beginning of the COVID-19 pandemic, using a facemask in different locations was recommended to slow down the spread of the virus. To evaluate facemasks9 performance, masks9 filtration efficiency is tested for a range of particle sizes. Although such tests quantify the blockage of the mask for a range of particle sizes, the test does not quantify the cumulative amount of virus-laden particles inhaled or exhaled by its wearer. In this study, we quantify the accumulated viruses that the healthy person inhales as a function of time, activity level, type of mask, and room condition using a physics-based model. We considered different types of masks, such as surgical masks and filtering facepieces (FFPs), and different characteristics of public places such as office rooms, buses, trains, and airplanes. To do such quantification, we implemented a physics-based model of the mask. Our results confirm the importance of both people wearing a mask compared to when only one wears the mask. The protection time before the healthy wearer has an infection risk of 50% reduces by 80% if only one wears the facemask instead of both people. The protection time is further reduced if the infected person starts to cough or increases the activity level by 85% and 99%, respectively. Results show the leakage of the mask can considerably affect the performance of the mask. For the surgical mask, the apparent filtration efficiency reduces by 75% with such a leakage, which cannot provide sufficient protection despite the high filtration efficiency of the mask. The facemask model presented provides key input in order to evaluate the protection of masks for different conditions in public places. The physics-based model of the facemask is provided as an online application.
Background. The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relates to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections. Methods. Among 11822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 31 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons Results. Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups. Conclusions. The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age.
Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine ̶ either heterologous (PHH-1V group) or homologous (BNT162b2 group) ̶ in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies against the ancestral Wuhan-Hu-1 strain and different variants of SARS-CoV-2 after the PHH-1V or the BNT162b2 boost, the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides and the safety and tolerability of PHH-1V as a boost. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001) and 0.87 (p=0.43) for the ancestral Wuhan-Hu-1 strain; 0.61 (p<0.0001) and 0.57 (p=0.0064) for the beta variant; 1.01 (p=0.89) and 0.52 (p=0.0003) for the delta variant; and 0.59 (p=<0.0001) and 0.56 (p=0.0026) for the omicron variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, elicits a strong and sustained neutralizing antibody response against Wuhan-Hu-1 strain, and a superior one concerning the previous circulating beta and delta SARS-CoV-2 variants, as well as the currently circulating omicron. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
Multiple studies across global populations have established the primary symptoms characterising COVID-19 (Coronavirus Disease 2019) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups (9no COVID-199, 9COVID-19 in last 12 weeks9, 9COVID-19 > 12 weeks ago9), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 9COVID-19 in last 12 week,9 and 9no COVID-199 groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 9COVID-19 > 12 weeks ago9 and 9no COVID-199 groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.
Background. The elderly are highly vulnerable to severe Covid-19. Waning immunity and emergence of Omicron have caused concerns about reduced effectiveness of Covid-19 vaccines. The objective was to estimate vaccine effectiveness (VE) against severe Covid-19 among the elderly. Methods. This nationwide, register-based cohort analysis included all residents aged 70 years and over in Finland. The follow-up started on December 27, 2020, and ended on March 31, 2022. The outcomes of interest were Covid-19-related hospitalization and intensive care unit (ICU) admission timely associated with SARS-CoV-2 infection. VE was estimated as one minus the hazard ratio comparing the vaccinated and unvaccinated and taking into account time since vaccination. Omicron-specific VE was evaluated as the effectiveness observed since January 1, 2022. Results. The cohort included 896220 individuals. Comirnaty (BioNTech/Pfizer) VE against Covid-19-related hospitalization was 93% (95% CI 89%-95%) and 85% (95% CI 82%-87%) 14-90 and 91-180 days after the second dose; VE increased to 95% (95% CI 94%-96%) 14-60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe Covid-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 98% (95% CI 92%-99%) and 92% (95% CI 87%-95%) 14-90 and 91-180 days after the second and 98% (95% CI 95%-99%) 14-60 days after the third dose. Conclusions. VE against severe Covid-19 is high among the elderly. It waned slightly after two doses, but a third restored the protection. VE against severe Covid-19 remained high even after the emergence of Omicron.
The emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 in late 2021 was followed by a marked increase of breakthrough infections. Estimates of vaccine effectiveness (VE) in the long term are key to assess potential resurgence of COVID-19 cases in the future. We conducted a systematic review of manuscripts published until June 21, 2022 to identify studies reporting the level of protection provided by COVID-19 vaccines against SARS-CoV-2 infection and symptomatic disease at different time points since vaccine administration. An exponential model was used to perform a secondary data analysis of the retrieved data to estimate the progressive waning of VE associated with different vaccine products, numbers of received doses, and SARS-CoV-2 variants. Our results show that VE of BNT162b2, mRNA-1273, ChAdOx1 nCoV-19 vaccines against any laboratory confirmed infection with Delta might have been lower than 70% at 9 months from second dose administration. We found a marked immune escape associated with Omicron infection and symptomatic disease, both after the administration of two and three doses. The half-life of protection against symptomatic infection provided by two doses was estimated in the range of 178-456 days for Delta, and between 66 and 73 days for Omicron. Booster doses were found to restore the VE to levels comparable to those acquired soon after administration of the second dose; however, a fast decline of booster VE against Omicron was observed, with less than 20% VE against infection and less than 25% VE against symptomatic disease at 9 months from the booster administration. This study provides a cohesive picture of the waning of vaccine protection; obtained estimates can inform the identification of appropriate targets and timing for future COVID-19 vaccination programs.
Importance: Diabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, available studies lack detail on COVID illness severity and measurement of relevant comorbidities. Design, Setting, and Participants: We conducted a multicenter, retrospective cohort study of patients over the age of 18 years who were hospitalized with COVID-19 between January 1, 2020 and November 30, 2020 in Ontario, Canada and Copenhagen, Denmark. Chart abstraction emphasizing co-morbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poissson regression. Main Outcomes and Measures: within hospital 30-day risk of death. Results: Our study included 1018 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients respectively had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older, have chronic kidney disease, cardiovascular disease, higher troponin levels, and to receive antibiotics compared with adults who did not have diabetes. In Ontario, the crude mortality rate ratio among patients with diabetes was 1.60 [1.24 — 2.07 95% CI] and in the adjusted regression model was 1.20 [0.86 — 1.66 95% CI]. In Denmark, the crude mortality rate ratio among patients with diabetes was 1.27 (0.68 — 2.36 95% CI) and in the adjusted model was 0.90 (0.49 — 1.54 95% CI)]. Meta-analyzing the two rate ratios from each region resulted in a crude mortality rate ratio of 1.55 (95% CI 1.22,1.96) and an adjusted mortality rate ratio of 1.11 (95% CI 0.84, 1.47). Conclusions: Presence of diabetes was not strongly associated with in-hospital COVID mortality independent of illness severity and other comorbidities.
Antibody titers wane after two-dose COVID-19 vaccinations, but individual variation in vaccine-elicited antibody dynamics remains to be explored. Here, we created a personalized antibody score that enables individuals to infer their antibody status by use of a simple calculation. We recently developed a mathematical model of B cell differentiation to accurately interpolate the longitudinal data from a community-based cohort in Fukushima, Japan, which consists of 2,159 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time course of the vaccine- elicited antibody response, we first elucidated individual background factors that contributed to the main features of antibody dynamics, i.e., the peak, the duration, and the area under the curve. We found that increasing age was a negative factor and a longer interval between the two doses was a positive factor for individual antibody level. We also found that the presence of underlying disease and the use of medication affected antibody levels negatively, whereas the presence of adverse reactions upon vaccination affected antibody levels positively. We then applied to these factors a recently proposed computational method to optimally fit clinical scores, which resulted in an integer-based score that can be used to evaluate the antibody status of individuals from their basic demographic and health information. This score can be easily calculated by individuals themselves or by medical practitioners. There is a potential usefulness of this score for identifying vulnerable populations and encouraging them to get booster vaccinations.
Background At the time of this study, Massachusetts had recorded a total of 352,558 COVID-19 cases and 12,076 deaths. Few qualitative studies have been conducted that investigate the experiences of university students and employees during the COVID-19 pandemic. The objective of this study was to explore the knowledge, attitudes, and practices regarding COVID-19 in university affiliates to inform future COVID-19 policies. Methods Semi-structured focus groups and interviews were conducted via Zoom between December 14, 2020 and January 15, 2021. Twenty-two focus group participants included undergraduate students, graduate students and university employees who had not experienced isolation or quarantine during the Fall 2020 semester. Fourteen participants who had experienced quarantine or isolation were interviewed individually to protect confidentiality. Data were analyzed using Dedoose software via inductive thematic analysis, with reporting as per Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines. Results Five major themes emerged from these data: COVID-19 knowledge, stress and coping, trust, decision-making, and institutional feedback. Misinformation regarding COVID-19 was common, compounding high levels of stress reported by many participants. Reported direct sources of stress included physical illness, fear of infection, and lack of access to resources while in quarantine or isolation settings. Reported indirect sources of stress included social isolation and financial constraints. Levels of trust were generally high regarding mainstream news media, scientific journals, and university-related information sources. For decision-making processes, participants described altered behaviors to socialize safely during the pandemic, which included increased testing, gathering outdoors, and limiting group sizes. Conversely, some undergraduate students reported increases in socialization behaviors after testing negative for COVID-19, while most university employees did not report altered behaviors after negative test results. While some participants described negative feedback regarding university decisions, most feedback for the institution was positive, with participants reporting appreciation for the university9s asymptomatic testing program and other on-campus health response activities. Conclusion The university9s investment in COVID-related resources, including the asymptomatic testing program and the on-campus quarantine and isolation spaces, were reported to greatly reduce stress and increase perceived safety. Key findings from this research could guide institutional communication, public health protocols, and support for university community members.
Background: The most common cause of death in people with COVID-19 is acute respiratory distress syndrome (ARDS). ARDS is a heterogeneous syndrome, however subgroups that have been identified among non-COVID-19 ARDS patients do not clearly apply to COVID-19 ARDS patients. Additionally, studies of COVID-19 ARDS have been limited by sample size. Methods: We applied an iterative clustering and machine learning framework to electronic health record data from thousands of hospitalized COVID-19 ARDS patients with the goal of defining and characterizing clinically-relevant COVID-19 ARDS subgroups (phenoclusters). We then applied a supervised model to identify risk factors for hospital mortality for each phenocluster and compared these between phenoclusters and the entire cohort. Findings: Risk factors that predict mortality in the overall cohort of COVID-19 ARDS patients do not necessarily predict mortality in phenoclusters. In fact, some risk factors increase the risk of hospital mortality in some phenoclusters, but decrease in others. Interpretation: These phenocluster-specific risk factors would not have been observed with a single predictive model; therefore, it is critical to: (1) cluster patients based on attributes, and (2) model within a cluster to discover the drivers of mortality.
Whether an outbreak of infectious disease is likely to grow or dissipate is determined through the time-varying reproduction number, Rt. Real-time or retrospective identification of changes in Rt following the imposition or relaxation of interventions can thus contribute important evidence about disease transmission dynamics which can inform policymaking. Here, we present a method for estimating shifts in Rt within a renewal model framework. Our method, which we call EpiCluster, is a Bayesian nonparametric model based on the Pitman-Yor process. We assume that Rt is piecewise-constant, and the incidence data and priors determine when or whether Rt should change and how many times it should do so throughout the series. We also introduce a prior which induces sparsity over the number of changepoints. Being Bayesian, our approach yields a measure of uncertainty in Rt and its changepoints. EpiCluster is fast, straightforward to use, and we demonstrate that it provides automated detection of rapid changes in transmission, either in real-time or retrospectively, for synthetic data series where the Rt profile is known. We illustrate the practical utility of our method by fitting it to case data of outbreaks of COVID-19 in Australia and Hong Kong, where it finds changepoints coinciding with the imposition of non-pharmaceutical interventions. Bayesian nonparametric methods, such as ours, allow the volume and complexity of the data to dictate the number of parameters required to approximate the process and should find wide application in epidemiology.
Background The global pandemic of COVID-19 infections continues to grow worldwide, with rising number of deaths day by day. The hyperinflammation state contributes to the multiorgan failure associated with COVID-19 infections. This study aims to explore the efficacy and safety of anakinra in COVID-19 patients with both respiratory distress and cytokine release syndromes. Methods This was an open-label, multicenter, randomized clinical trial. Patients were randomized in 1:1 ratio to receive standard of care (SOC) alone, or anakinra plus SOC. Adults with confirmed COVID-19 infection with evidence of both respiratory distress and cytokine release syndrome were included. The primary outcome was treatment success at day 14, defined as WHO clinical progression score of ≤3. The primary analysis was based on intention-to-treat population, with p-value of <0.05. Results A total of 80 patients were enrolled in the study. The mean age was 49.9 years (SD=11.7), with 82.5% (n=66) male patients. The primary outcome was not statistically different (87.5% (n=35) in anakinra group vs. 92.5% (n=37) in SOC group, p=0.712). The majority of reported adverse events were mild in severity and not related to the study treatment. Increased aspartate aminotransferase was the only significant adverse event (35% (n=14) in anakinra group vs. 15% (n=6) in SOC group, p=0.039); yet, was not associated with treatment discontinuation. Conclusion In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was not associated with significant improvement in the WHO clinical progression scale. Further studies investigating patients9 subgroups that might benefit from anakinra are warranted. The trial was registered at ClinicalTrials.gov (NCT04643678).
Immuno-bridging Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition: COVID-19
Interventions: Biological: COVID-19 Protein Subunit Recombinant Vaccine; Biological: Active Comparator
Sponsors: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; Faculty of Medicine Universitas Diponegoro; Faculty of Medicine Universitas Andalas; Faculty of Medicine Universitas Hassanudin
Recruiting
A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised - Condition: COVID-19
Interventions: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir
Sponsor: Pfizer
Not yet recruiting
A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa. - Condition: COVID-19
Interventions: Device: Abbott Panbio rapid antigen self-tests; Other: COVIDSmart CARE! app
Sponsors: McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Cape Town Lung Institute
Not yet recruiting
Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition: COVID-19
Interventions: Drug: FB2001; Drug: FB2001 placebo
Sponsor: Frontier Biotechnologies Inc.
Not yet recruiting
Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated - Condition: COVID-19
Interventions: Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain; Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors: Sinovac Biotech (Colombia) S.A.S.; Sinovac Life Sciences Co., Ltd.
Not yet recruiting
A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition: COVID-19
Interventions: Drug: PanCytoVir™ (probenecid); Drug: Placebo
Sponsor: TrippBio, Inc.
Not yet recruiting
Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition: Post-COVID19 Condition
Interventions: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure
Sponsors: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits
Not yet recruiting
IMM-BCP-01 in Mild to Moderate COVID-19 - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Drug: IMM-BCP-01; Drug: Placebo
Sponsors: Immunome, Inc.; United States Department of Defense
Recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1) - Condition: COVID-19
Intervention: Biological: ABO1009-DP
Sponsor: Suzhou Abogen Biosciences Co., Ltd.
Not yet recruiting
A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines - Condition: COVID-19
Interventions: Biological: ABO1009-DP; Biological: ABO-CoV.617.2; Other: Placebo
Sponsor: Suzhou Abogen Biosciences Co., Ltd.
Not yet recruiting
Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions: COVID-19; Dysglycemia
Interventions: Drug: Insulin; Drug: Subcutaneous Insulin
Sponsor: Benha University
Completed
A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine - Condition: COVID-19
Interventions: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine
Sponsor: CanSino Biologics Inc.
Not yet recruiting
Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19 - Conditions: COVID-19; COVID-19 Respiratory Infection; Long COVID
Interventions: Diagnostic Test: Low-field magnetic resonance imaging; Diagnostic Test: Nailfold capillaroscopy; Diagnostic Test: Spiroergometry; Diagnostic Test: Realtime deformability cytometry
Sponsor: University of Erlangen-Nürnberg Medical School
Recruiting
Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19. - Conditions: COVID-19 Pneumonia; COVID-19
Interventions: Biological: Mesenchymal stem cell; Other: Placebo
Sponsors: Paulo Brofman; Conselho Nacional de Desenvolvimento Científico e Tecnológico
Recruiting
Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients - Conditions: Tension-Type Headache; Orofacial Pain; COVID-19
Intervention: Radiation: Photobimodulation
Sponsor: University of Nove de Julho
Recruiting
Specificity and Confirmation of SARS-CoV-2 Serological Test Methods in Emergency Department Populations across the United States - CONCLUSIONS: The specificity of the serological assays evaluated in a large, diverse emergency department population was >99% and did not vary by geographical site. A confirmatory algorithm with an automated pseudo-neutralization assay allowed testing on the same specimen while reducing the false positivity rate and increasing the value of serology screening methods.
Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases - INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses.
Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals - Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects…
Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections - Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines….
Title: Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry - Saliva contributes to the innate immune system, which suggests that it can prevent SARS-CoV-2 entry. We studied the ability of healthy salivary proteins to bind to angiotensin-converting enzyme 2 (ACE2) using biolayer interferometry and pull-down assays. Their effects on binding between the receptor-binding domain of the SARS-CoV-2 spike protein S1 (S1) and ACE2 were determined using an enzyme-linked immunosorbent assay. Saliva bound to ACE2 and disrupted the binding of S1 to ACE2 and four…
Current status and prospects of IL-6-targeting therapy - INTRODUCTION: Persistent and excess IL-6 production often contributes to a variety of immune diseases. IL-6-targeting therapy was first approved for Castleman disease, then rheumatoid arthritis, and now it is broadly used. Furthermore, it has been approved not only for chronic and acute inflammatory diseases but also for autoantibody-induced diseases such as neuromyelitis optica spectrum disorder and interstitial lung disease due to systemic sclerosis.
In vitro evaluation of antiviral activity of Sisybrium irio (Khaksi) against SARS-COV-2 - SARS-CoV-2 pandemic, drawn attention to the need of virus culture. In vitro SARS-COV-2 culture was performed to carry out therapeutic, environmental and virus genome studies. Isolation of virus from nasopharyngeal swab was performed by inoculating virus positive samples in available cell lines. SARS-CoV-2 topography was observed by using Scanning Electron Microscopy (SEM). Virus specificity was defined by serological confirmation through neutralization assay with COVID 19 convalescent sera. The…
An outlook on potential protein targets of COVID-19 as a druggable site - CONCLUSION: Using cryo-electron microscopy or X-ray diffraction, hundreds of crystallographic data of SARS-CoV-2 proteins have been published including structural and non-structural proteins. These proteins have a significant role at different aspects in the viral machinery and presented themselves as potential target for drug designing and therapeutic interventions. Also, there are few host cell proteins which helps in SARS-CoV-2 entry and proteolytic cleavage required for viral infection.
Istradefylline, an adenosine A2a receptor antagonist, inhibits the CD4+ T-cell hypersecretion of IL-17A and IL-8 in humans - Extracellular adenosine produced from ATP plays a role in energy processes, neurotransmission, and inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson’s disease. We previously showed using mouse models that adenosine primes hypersecretion of interleukin (IL)-17A via A2aR, which plays a role in neutrophilic inflammation models in mice. This finding suggests that adenosine is an endogenous modulator of neutrophilic…
THE COVID-19 ORAL DRUG MOLNUPIRAVIR IS A CES2 SUBSTRATE: POTENTIAL DRUG-DRUG INTERACTIONS AND IMPACT OF CES2 GENETIC POLYMORPHISM IN VITRO - Molnupiravir is one of the two COVID-19 oral drugs that were recently granted the emergency use authorization by the Food and Drug Administration (FDA). Molnupiravir is an ester and requires hydrolysis to exert antiviral activity. Carboxylesterases constitute a class of hydrolases with high catalytic efficiency. Humans express two major carboxylesterases (CES1 and CES2) that differ in substrate specificity. Based on the structural characteristics of molnupiravir, this study was performed to…
Low Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients - CONCLUSION: Mild AATD (PIMS or PIMZ) was rare in a small cohort of hospitalized patients with COVID-19 in a study setting with a high background prevalence of AATD.
Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2 - SARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19), progressively extended worldwide countries on an epidemic scale. Along with all the drug treatments suggested to date, currently, there are no approved management protocols and treatment regimens for SARS-CoV-2. The unavailability of optimal medication and effective vaccines against SARS-CoV-2 indicates the requirement for alternative therapies. Probiotics are living organisms that deliberate beneficial effects on the host when…
Skills-approximate occupations: using networks to guide jobs retraining - An issue often confronting economic development agencies is how to minimize unemployment due to disruptions like technological change, trade wars, recessions, or other economic shocks. Decision makers are left to craft policies that can absorb surplus labor with as little pain to workers as possible. The questions they face include how to re-employ displaced workers and how to fill labor shortages. To address such questions, we quantify the proximity of any two occupations based on the skills…
Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine Sulfated Glycans - The COVID-19 pandemic has steered the global therapeutic research efforts towards the discovery of potential anti-SARS-CoV-2 molecules. The role of the viral spike glycoprotein (S-protein) has been clearly established in SARS-CoV-2 infection through its capacity to bind to the host cell surface heparan sulfate proteoglycan (HSPG) and angiotensin-converting enzyme-2 (ACE2). The antiviral strategies targeting these two virus receptors are currently under intense investigation. However, the rapid…
JAK Inhibition as a New Treatment Strategy for Patients with COVID-19 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic continues to spread globally. The rapid dispersion of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 drives an urgent need for effective treatments, especially for patients who develop severe pneumonia. The excessive and uncontrolled release of pro-inflammatory cytokines has proved to be an essential factor in the rapidity of disease progression, and some cytokines are significantly associated with adverse…